Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.
This invention relates to a method for production of a radioactive aerosol such as carbon-encapsulated technetium-labelled nanoparticle-composites that can be used in medical diagnostics for gamma scintigraphy imaging of the interior of the lungs of a patient suffering from an airway dysfunction. Methods for production of carbon-encapsulated technetium-labelled nanoparticle-composites are well known.
U.S. Pat. No. 5,064,634 to Burch entitled “Method of Forming a Radioactive Metallic Vapor” and U.S. Pat. No. 5,228,444 to Burch entitled “Device for Producing a Gas-Lite Radionuclide Composition” discloses a method and apparatus for production of such inhalable radionuclide labelled aerosols. In particular, there is described a carbon crucible heated to a temperature within the range of 1500° to 2500° Celsius. The resulting aerosol product was later found to consist of the nanoparticle-composite described by Senden et al, (J. Nuclear Med. 38:1327-33, 1997) who also reported on incorporation of other isotopes. The product has been found suitable for use as a radioactive aerosol that can be used in medical diagnostics for gamma scintigraphy imaging of the interior of the lungs of a patient suffering from an airway dysfunction.
U.S. Pat. No. 5,792,241 to Browitt entitled “Precipitator” discloses a method and apparatus for dispersing the nanoparticle-composite into an aqueous medium.
The methods of production of carbon-encapsulated technetium-labelled nanoparticle-composites in the above prior art have a number of disadvantages.                1) The method of loading of the generator's carbon crucible with radionuclide is typically limited to evaporation of a radionuclide solution or direct addition of a solid. Using vapour phase particle sizing with appropriate instrumentation it has now been unfortunately and surprisingly found that both of these methods give rise to considerable contamination of the aerosol with large (>200 nm diameter) sodium chloride particles originating from the saline solution used to elute technetium generators. Salt contamination can be particularly significant when multiple loadings of the crucible are employed to concentrate the radionuclide eluate of weaker or older technetium generators. Multiple loading (e.g. three times or more) is often used in the clinical setting, especially in countries where only low specific activity technetium generators (e.g. 60 GBq) are available. Clearly sodium chloride particles are water soluble and therefore rapidly dissolve on wet surfaces such as lung airways, and may be carriers of non-encapsulated technetium in soluble form. This can lead to poor imaging of the lungs.        2) Using the conditions as described in the prior art was found to produce aerosols contaminated with surprisingly large amounts of water-soluble free radionuclide. This is a result of the rapid sublimation of the more volatile sodium chloride expelling radionuclide from the crucible before carbon encapsulation occurs. Non-encapsulated radioactive contaminants in the aerosol can lead to the disadvantageous result that they dissolve on the surface of a patient's lungs and subsequently enter the blood circulation and lymphatics. It can be reasonably expected that contamination with soluble free radionuclide will degrade the quality of airway imaging, by diffusion of signal away from the inner surface of the lungs, thus decreasing the specific signal to noise ratio. More importantly, it also unnecessarily exposes the patient to a significant systemic dose of radionuclide that continues for some hours after the imaging procedure.        2) In U.S. Pat. No. 5,064,634, the disclosed enabling conditions for aerosol generation have been found to produce poor results. It is conjectured that resistive heating of the carbon crucible is not sufficient to yield optimal amounts of a suitable imaging product.        3) The only description given in U.S. Pat. No. 5,064,634 relating to the method of heating the crucible is that it should be heated “preferably to at least 2200° C.”. It has been found that particles formed using this temperature range as a guide can be contaminated with free radionuclide, again leading to image degradation and systemic dosing. Further, larger particles (>200 nm diameter) of unstructured carbon were found to form at some higher temperature ranges. Larger particles can be expected to give less favourable airway imaging, penetrating less distance into the lungs before adhering to airway surfaces.        4) The duration of crucible heating in the generator is not specified in U.S. Pat. No. 5,064,634, nor is the time the aerosol product is allowed to reside in the apparatus before inhalation by the patient. It has been found that these factors are critical in particle production.        